Abstract Free carnitine is essential to mitochondrial health by buffering the free acetyl-CoA pool and thereby maintaining energy production. It is also responsible for transporting long-chain fatty acids into the mitochondria for oxidation. Almost all the body’s carnitine is in muscle, and plasma concentrations do not reflect tissue content, but there are as yet no non-invasive techniques to assess muscle total or free carnitine. Here we describe a novel non-invasive postprocessing method, using standard 1 H magnetic resonance spectroscopy data, for quantifying muscle total and free carnitine concentrations, which includes an orientation-visibility and spectral fitting component, and consideration of interfering metabolites. We demonstrate the importance of the orientation correction even within one muscle group (accounting for up to 1.9-fold difference within one muscle group and 2.9-fold difference in signal between muscles), show its good reproducibility (CoV 8-12%), and validate the results with mass spectrometry measurements in muscle biopsy samples. We apply this method in a group of patients with genetic mitochondrial disease, to investigate the relationship between mitochondrial dysfunction and muscle lipid accumulation. As predicted muscle total and free carnitine were lower in patients with disease and correlated with the degree of mitochondrial dysfunction and lipid accumulation. Further, robust spatial correlations of total carnitine and muscle lipid imply heterogeneity in mitochondrial function. Our findings suggest that increasing muscle carnitine stores could ameliorate the metabolic effects of and disorders related to mitochondrial dysfunction. Furthermore, it has not usually been known in supplementation studies whether l-carnitine actually reached the target tissue. We suggest that this novel method has significant potential for informing on physiology and pathophysiology, and as a biomarker in monitoring treatment response, investigative drug discovery, and personalised medicine.

Intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and insulin-sensitive (athletes) states. Biochemical analysis of intramuscular triglyceride composition is confounded by extramyocellular triglycerides in biopsy samples, and hence the specific composition of IMCLs is unknown in these states. 1H magnetic resonance spectroscopy (MRS) can be used to overcome this problem. Thus, we used a recently validated 1H MRS method to compare the compositional saturation index (CH2:CH3) and concentration independent of the composition (CH3) of IMCLs in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic subjects with that of age- and gender-matched athletes (n = 14) and healthy controls (n = 41). The IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic subjects compared with controls but was similar in athletes and controls. IMCL CH2:CH3 was dependent on the IMCL concentration in the controls and, after adjusting the compositional index for quantity (CH2:CH3adj), could distinguish lipodystrophics from athletes. This CH2:CH3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO2max The association of insulin resistance with the accumulation of saturated IMCLs is consistent with a potential pathogenic role for saturated fat and the reported benefits of exercise and diet in insulin-resistant states.

Ectopic lipids are flexible lipid stores and can be influenced by various interventions. A distinction must be made between short-term change (within hours) and long-term change (within weeks to months). In this chapter, after a short summary of methods to assess ectopic lipids we shall mainly focus on the short-term changes and the corresponding interventions, i.e., dietary interventions and physical exercise.

Magnetic Resonance in MedicineVolume 86, Issue 6 p. 2891-2896 OBITUARY Richard R. Ernst, August 14, 1933, to June 4, 2021: “Standing on the shoulder of giants” Chris Boesch, Corresponding Author Chris Boesch christoph.boesch@med.unibe.ch orcid.org/0000-0001-8498-8543 University of Bern, Bern, Switzerland Correspondence Chris Boesch, University of Bern, University and Inselspital, Bern CH-3010, Switzerland. Email: christoph.boesch@med.unibe.chSearch for more papers by this author Chris Boesch, Corresponding Author Chris Boesch christoph.boesch@med.unibe.ch orcid.org/0000-0001-8498-8543 University of Bern, Bern, Switzerland Correspondence Chris Boesch, University of Bern, University and Inselspital, Bern CH-3010, Switzerland. Email: christoph.boesch@med.unibe.chSearch for more papers by this author First published: 07 September 2021 https://doi.org/10.1002/mrm.29006Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume86, Issue6December 2021Pages 2891-2896 RelatedInformation

Skeletal muscle phosphorus‐31 31P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31P MRS methods can probe it. Here we consider basic signal‐acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with 31P MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near‐infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and 1H MRS measurements) can help in the physiological/metabolic interpretation of 31P MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology.

To cover increasing energy demands during exercise, tricarboxylic cycle (TCA) flux in skeletal muscle is markedly increased, resulting in the increased formation of intramyocellular acetylcarnitine (AcCtn). We hypothesized that reduced substrate availability within the exercising muscle, reflected by a diminished increase of intramyocellular AcCtn concentration during exercise, might be an underlying mechanism for the impaired exercise performance observed in adult patients with growth hormone deficiency (GHD). We aimed at assessing the effect of 2 hours of moderately intense exercise on intramyocellular AcCtn concentrations, measured by proton magnetic resonance spectroscopy (1H-MRS), in seven adults with GHD compared to seven matched control subjects (CS). Compared to baseline levels AcCtn concentrations significantly increased after 2 hours of exercise, and significantly decreased over the following 24 hours (ANOVA p for effect of time = 0.0023 for all study participants; p = 0.067 for GHD only, p = 0.045 for CS only). AcCtn concentrations at baseline, as well as changes in AcCtn concentrations over time were similar between GHD patients and CS (ANOVA p for group effect = 0.45). There was no interaction between group and time (p = 0.53). Our study suggests that during moderately intense exercise the availability of energy substrate within the exercising muscle is not significantly different in GHD patients compared to CS.

Sucrose overfeeding increases intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid concentrations in healthy subjects. We hypothesized that these effects would be modulated by diet protein/fat content. Twelve healthy men and women were studied on two occasions in a randomized, cross-over trial. On each occasion, they received a 3-day 12% protein weight maintenance diet (WM) followed by a 6-day hypercaloric high sucrose diet (150% energy requirements). On one occasion the hypercaloric diet contained 5% protein and 25% fat (low protein-high fat, LP-HF), on the other occasion it contained 20% protein and 10% fat (high protein-low fat, HP-LF). IHCL and IMCL concentrations (magnetic resonance spectroscopy) and energy expenditure (indirect calorimetry) were measured after WM, and again after HP-LF/LP-HF. IHCL increased from 25.0 ± 3.6 after WM to 147.1 ± 26.9 mmol/kg wet weight (ww) after LP-HF and from 30.3 ± 7.7 to 57.8 ± 14.8 after HP-LF (two-way ANOVA with interaction: p < 0.001 overfeeding x protein/fat content). IMCL increased from 7.1 ± 0.6 to 8.8 ± 0.7 mmol/kg ww after LP-HF and from 6.2 ± 0.6 to 6.9 ± 0.6 after HP-LF, (p < 0.002). These results indicate that liver and muscle fat deposition is enhanced when sucrose overfeeding is associated with a low protein, high fat diet compared to a high protein, low fat diet.

Background: Overconsumption of energy-dense foods and sleep restriction are both associated with the development of metabolic and cardiovascular diseases, but their combined effects remain poorly evaluated. Objective: The aim of this study was to assess whether sleep restriction potentiates the effects of a short-term overfeeding on intrahepatocellular lipid (IHCL) concentrations and on glucose homeostasis. Design: Ten healthy subjects were exposed to a 6-d overfeeding period (130% daily energy needs, with 15% extra energy as sucrose and 15% as fat), with normal sleep (8 h sleep opportunity time) or sleep restriction (4 h sleep opportunity time), according to a randomized, crossover design. At baseline and after intervention, IHCL concentrations were measured by proton magnetic resonance spectroscopy, and a dual intravenous [6,6-H-2(2)]-, oral C-13-labeled glucose tolerance test and a polysomnographic recording were performed. Results: Overfeeding significantly increased IHCL concentrations (P-overfeeding < 0.001; overfeeding + normal sleep: + 53% +/- 16%). During the oral glucose tolerance test, overfeeding significantly increased endogenous glucose production (P-overfeeding = 0.034) and the oxidation of 13C-labeled glucose load (P-overfeeding = 0.038). Sleep restriction significantly decreased total sleep time, and the duration of stages 1 and 2 and rapid eye movement sleep (all P < 0.001), whereas slow-wave sleep duration was preserved (P-overfeeding x sleep = 0.809). Compared with overfeeding, overfeeding + sleep restriction did not change IHCL concentrations (P-overfeeding x sleep = 0.541; +83% +/- 33%), endogenous glucose production (P-overfeeding x sleep = 0.567), or exogenous glucose oxidation (P-overfeeding x sleep = 0.118). Sleep restriction did not significantly alter blood pressure, heart rate, or plasma cortisol concentrations (all P-overfeeding x sleep = NS). Conclusions: Six days of a high-sucrose, high-fat overfeeding diet significantly increased IHCL concentrations and increased endogenous glucose production, suggesting hepatic insulin resistance. These effects of overfeeding were not altered by sleep restriction. This trial was registered at clinicaltrials.gov as NCT02075723. Other study ID numbers: SleepDep 02/14.

Context Paradoxically, intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and to insulin-sensitive (athletes) states. The composition of this lipid store is unknown in these states.Design and Methods We used a recently validated and potentially widely applicable 1H magnetic resonance spectroscopy method to compare the compositional saturation index (CH2:CH3 ratio) and concentration independent of composition (CH3) of intramyocellular lipid in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic patients with that of age- and gender-matched athletes (n=14) and healthy controls (n = 41).Main Outcome IMCL compositional saturation index (CH2:CH3 ratio).Results The IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic patients compared with age- and gender-matched controls but not compared to athletes. IMCL CH2:CH3 was dependent on IMCL concentration in the controls and after adjusting the composition index for quantity (CH2:CH3adj) was able to distinguish patients from athletes. With groups pooled, this CH2:CH3adj marker had the strongest relation to insulin resistance (HOMA-IR) compared to other measures of lipid concentration and composition, especially in the soleus muscle. Contrary to the ‘athlete’s paradox’, IMCL in athletes was similar in tibialis anterior (p>0.05) and significantly lower in the soleus (p < 0.004) compared to both controls and patients.Conclusions The IMCL saturation index adjusted for quantity, which likely reflects accumulation of saturated IMCL, is more closely associated with insulin resistance than concentration alone.

PurposeTo combine the metabolite‐cycling technique with diffusion‐weighted 1H‐MR spectroscopy and to use the inherent water reference for compensation of motion‐related signal loss for improved estimation of metabolite apparent diffusion coefficients (ADCs).MethodsDiffusion‐weighted spectra of water and metabolites were acquired simultaneously using metabolite‐cycling at 3 T. The water information was used for signal correction of phase, frequency, and eddy currents, as well as for compensation of motion‐induced signal loss. ADCs were estimated by 2D simultaneous fitting. The quality of ADC restoration was investigated in vitro. Subsequently, the new approach was applied in 13 subjects for enhanced metabolite ADC estimation in gray matter.ResultsMetabolite‐cycled diffusion 1H‐MRS is suitable to measure metabolite and water ADCs simultaneously. The water reference facilitates signal amplitude restoration, compensating for motion‐related artefacts. 2D fitting stabilizes the fitting procedure and allows the estimation of ADCs even for low signal‐to‐noise metabolites. Use of the motion‐compensation scheme leads to estimation of smaller ADCs for virtually all metabolites (44% smaller ADC on average), to a reduction of fitting uncertainties for metabolite ADCs in individual subjects and reduced variance over the cohort (45% smaller SD on average).ConclusionUsing the simultaneously acquired water signal as internal reference allows not only for compensation of phase and frequency fluctuations but also for signal amplitude restoration, and thus improved metabolite ADC estimation. Combination with 2D simultaneous fitting promises access to the diffusion properties even for low signal‐to‐noise metabolites. The combination of both techniques increases the specificity and sensitivity of estimated metabolite ADC values in the cohort.

Background: Ectopic lipids such as intramyocellular lipids (IMCL) are depleted by exercise and repleted by diet, whereas intrahepatocellular lipids (IHCL) are increased immediately after exercise. So far, it is unclear how ectopic lipids behave 24 h after exercise and whether the lack of growth hormone (GH) significantly affects ectopic lipids 24 h after exercise. Methods: Seven male patients with growth hormone deficiency (GHD) and seven sedentary male control subjects (CS) were included. VO2max was assessed by spiroergometry; visceral and subcutaneous fat by whole body MRI. H-1-MR-spectroscopy was performed in M. vastus intermedius and in the liver before and after 2 h of exercise at 50% VO2max and 24 h thereafter, while diet and physical activity were standardized. Results: Sedentary male subjects (7 GHD, 7 CS) were recruited. Age, BMI, waist circumference, visceral and subcutaneous fat mass was not significantly different between GHD and CS. VO2max was significantly lower in GHD vs. CS. IMCL were diminished through aerobic exercise in both groups: (-11.5 +/- 21.9% in CS; -8.9% +/- 19.1% in GHD) and restored after 24 h in CS (-5.5 +/- 26.6% compared to baseline) but not in GHD (-17.9 +/- 15.3%). IHCL increased immediately after exercise and decreased to baseline within 24 h. Conclusion: These findings suggest that GHD may affect repletion of IMCL 24 h after aerobic exercise.

Intramyocellular lipid (IMCL) is of particular metabolic interest, but despite many proton magnetic resonance spectroscopy ( 1 H MRS) studies reporting IMCL content measured by the methylene (CH 2 ) resonance signal, little is known about its composition. Here we validated IMCL CH 3 :CH 2 ratio as a compositional marker using 1 H MRS at short echo time, and investigated IMCL content and composition during a 28-hour fast in 24 healthy males. Increases in IMCL CH 2 relative to the creatine and phosphocreatine resonance (Cr) at 3.0 ppm (an internal standard) correlated with circulating free fatty acid (FA) concentrations, supporting the concept of increased FA influx into IMCL. Significant decreases in IMCL CH 3 :CH 2 ratio indicated a less unsaturated IMCL pool after fasting, and this compositional change related inversely to IMCL baseline composition, suggesting a selective efflux of unsaturated shorter-chain FA from the IMCL pool. This novel in vivo evidence reveals IMCL turnover during extended fasting, consistent with the concept of a flexible, responsive myocellular lipid store. There were also differences between soleus and tibialis anterior in basal IMCL composition and in response to fasting. We discuss the potential of this marker for providing insights into normal physiology and mechanisms of disease.

HomeRadiologyVol. 286, No. 2 PreviousNext Reviews and CommentaryEditorialQuantitative MR Imaging Is Increasingly Important in Liver DiseaseChris Boesch Chris Boesch Author AffiliationsFrom the Departments of Radiology and Clinical Research, University and Inselspital Bern, AMSM (DKF-DIPR), Erlachstrasse 9A, CH-3012 Bern, Switzerland.Address correspondence to the author (e-mail: [email protected]).Chris Boesch Published Online:Jan 22 2018https://doi.org/10.1148/radiol.2017172312MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References1. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013;10(11):686–690. Crossref, Medline, Google Scholar2. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology doi: 10.1002/hep.29367. Published online July 17, 2017. Accessed September 17, 2017. Google Scholar3. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;64(6):1388–1402. Crossref, Medline, Google Scholar4. Benedict M, Zhang X. Non-alcoholic fatty liver disease: an expanded review. World J Hepatol 2017;9(16):715–732. Crossref, Medline, Google Scholar5. Runge JH, Smits LP, Verheij J, et al. MR spectroscopy–derived proton density fat fraction is superior to controlled attenuation parameter for detecting and grading hepatic steatosis. Radiology 2018;286(2):547–556. Link, Google Scholar6. Ratziu V, Charlotte F, Heurtier A, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128(7):1898–1906. Crossref, Medline, Google Scholar7. Karlas T, Petroff D, Garnov N, et al. Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and 1H-MR spectroscopy. PLoS One 2014;9(3):e91987. Crossref, Medline, Google Scholar8. Imajo K, Kessoku T, Honda Y, et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology 2016;150(3):626–637.e7. Crossref, Medline, Google Scholar9. Yokoo T, Serai SD, Pirasteh A, et al. Linearity, bias, and precision of hepatic proton density fat fraction measurements by using MR imaging: a meta-analysis. Radiology doi: 10.1148/radiol.2017170550. Published online September 11, 2107. Accessed September 17, 2017. Google Scholar10. Kukuk GM, Hittatiya K, Sprinkart AM, et al. Comparison between modified Dixon MRI techniques, MR spectroscopic relaxometry, and different histologic quantification methods in the assessment of hepatic steatosis. Eur Radiol 2015;25(10):2869–2879. Crossref, Medline, Google Scholar11. de Lédinghen V, Wong GL, Vergniol J, et al. Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2016;31(4):848–855. Crossref, Medline, Google Scholar12. Muthupillai R, Lomas DJ, Rossman PJ, Greenleaf JF, Manduca A, Ehman RL. Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. Science 1995;269(5232):1854–1857. Crossref, Medline, Google ScholarArticle HistoryReceived October 11, 2017; final version accepted October 12.Published online: Jan 22 2018Published in print: Feb 2018 FiguresReferencesRelatedDetailsCited ByBrazilian Society of Hepatology and Brazilian College of Radiology practice guidance for the use of elastography in liver diseasesAna CarolinaCardoso, CristianeA. Villela-Nogueira, Cláudiode Figueiredo-Mendes, HiltonLeão Filho, Rogério AugustoPinto Silva, CristianeValle Tovo, HugoPerazzo, Antonio CarlosMatteoni, Roberto Joséde Carvalho-Filho, PauloLisboa Bittencourt2021 | Annals of Hepatology, Vol. 22Development and validation of radiomics model built by incorporating machine learning for identifying liver fibrosis and early-stage cirrhosisQing-TaoQiu, JingZhang, Jing-HaoDuan, Shi-ZhangWu, Jia-LinDing, YongYin2020 | Chinese Medical Journal, Vol. 133, No. 22Recommended Articles MR Spectroscopy–derived Proton Density Fat Fraction Is Superior to Controlled Attenuation Parameter for Detecting and Grading Hepatic SteatosisRadiology2017Volume: 286Issue: 2pp. 547-556Multiparametric US for Identifying Patients with High-Risk NASH: A Derivation and Validation StudyRadiology2021Volume: 301Issue: 3pp. 625-634Detection of Steatohepatitis in a Rat Model by Using Spectroscopic Shear-Wave US ElastographyRadiology2016Volume: 282Issue: 3pp. 726-733Liver Stiffness in Pediatric Patients with Fatty Liver Disease: Diagnostic Accuracy and Reproducibility of Shear-Wave ElastographyRadiology2016Volume: 283Issue: 3pp. 820-827US-derived Fat Fraction Screening of Hepatic SteatosisRadiology2022Volume: 304Issue: 1pp. 83-84See More RSNA Education Exhibits The Role of Imaging in Quantitative Assessment of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease: Focus on Quantitative Ultrasound ApproachesDigital Posters2019Ultrasound Quantification Of Liver Fat: Past, Present, And FutureDigital Posters2021The Many Faces Of The Fat Liver: A Guide To Recognize All Patterns Of Non-alcoholic Fatty Liver Disease (NAFLD) On Multiparametric Hepatic MRIDigital Posters2021 RSNA Case Collection Hepatic SteatosisRSNA Case Collection2021LI-RADS 5RSNA Case Collection2022Multifocal hepatic steatosis RSNA Case Collection2020 Vol. 286, No. 2 Metrics Altmetric Score PDF download

Objective Simultaneous modeling of true 2-D spectroscopy data, or more generally, interrelated spectral datasets has been described previously and is useful for quantitative magnetic resonance spectroscopy applications. In this study, a combined method of reference-lineshape enhanced model fitting and two-dimensional prior-knowledge fitting for the case of diffusion weighted MR spectroscopy is presented. Materials and methods Time-dependent field distortions determined from a water reference are applied to the spectral bases used in linear-combination modeling of interrelated spectra. This was implemented together with a simultaneous spectral and diffusion model fitting in the previously described Fitting Tool for Arrays of Interrelated Datasets (FiTAID), where prior knowledge conditions and restraints can be enforced in two dimensions. Results The benefit in terms of increased accuracy and precision of parameters is illustrated with examples from Monte Carlo simulations, in vitro and in vivo human brain scans for one- and two-dimensional datasets from 2-D separation, inversion recovery and diffusion-weighted spectroscopy (DWS). For DWS, it was found that acquisitions could be substantially shortened. Conclusion It is shown that inclusion of a measured lineshape into modeling of interrelated MR spectra is beneficial and can be combined also with simultaneous spectral and diffusion modeling.

We examined whether waist circumference (WC) is associated with liver fat in black and white adolescents. Liver fat was measured using a 3T proton magnetic resonance spectroscopy (1H-MRS) in 152 overweight/obese adolescents (94 black and 58 white, body mass index (BMI) ≥85th percentile, aged 12-18 years) without liver diseases or diabetes. WC was measured at the last rib. Total and visceral adipose tissue (VAT) were measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, respectively. The proportion of fatty liver (defined as liver fat ≥5.0% by 1H-MRS) was lower (P < 0.01) in black adolescents (5.3%) compared with their white peers (24.1%). Despite similar age, BMI, WC, and total adiposity (%), black adolescents had lower (P < 0.01) VAT (59.0% vs. 81.3 cm2), liver fat (1.6% vs. 3.5%), and alanine aminotransferase (17.2 vs. 22.0 IU/L) compared with their white peers. Independent of race, WC was associated with liver fat (black, r = 0.43; white, r = 0.64) in a similar magnitude to the association between VAT and liver fat (black, r = 0.44; white, r = 0.51) and these findings remained significant after controlling for age, sex, Tanner stage, and total adiposity. In blacks, WC and sex (male) were independent (P < 0.01) predictors of liver fat, explaining 17.1% and 5.6% of the variance, respectively, while in whites WC was the single best predictor, explaining 40.8% of the variance in liver fat. These findings suggest that enlarged WC is a marker of increased liver fat in overweight/obese white and black adolescents.

Objective: Addition of fructose to the diet of normal weight and overweight subjects can increase postprandial plasma triglyceride and uric acid concentration. We, therefore, assessed whether replacing sugar-sweetened beverages (SSB) with artificially-sweetened beverages (ASB) in the diet of overweight and obese subjects would decrease these parameters. Methods: Twenty-six participants of the REDUCS study, which assessed the effects of replacing SSB by ASB over 12 weeks on intra-hepatocellular lipid concentration, were included in this sub-analysis. All were studied after a four-week run-in period during which they consumed their usual diet and SSBs, and after a 12-week intervention in which they were randomly assigned to replace their SSBs with ASBs (ASB arm) or to continue their usual diet and SSBs (control arm, CTRL). At the end of run-in (week 4) and again at the end of intervention (week 16), they took part in an 8.5 h metabolic investigation during which their plasma glucose, insulin, glucagon, lactate, triglyceride (TG), non-esterified fatty acids (NEFA), and uric acid concentrations were measured over a 30 min fasting period (−30–0 min), then every 2 h over 480 min. with ingestion of standard breakfast at time 0 min and a standard lunch at time 240 min. Breakfast and lunch were consumed together with a 3.3 dL SSB at week 4 and with either an ASB (ASB arm) or a SSB (CTRL arm) at week 16. After analyzing the whole group, a secondary analysis was performed on 14 subjects with hepatic steatosis (seven randomized to ASB, seven to CTRL) and 12 subjects without hepatic steatosis (six randomized to ASB and six to CTRL). Results: Ingestion of meals increased plasma glucose, insulin, glucagon, lactate, and TG concentrations and decreased NEFA concentrations, but with no significant difference of integrated postprandial responses between week 4 and week 16 in both ASB and CTRL, except for a slightly decreased glucagon response in ASB. There was, however, no significant postprandial increase in uric acid concentration in both arms. In the secondary analysis, replacing SSBs with ASBs did not significantly change postprandial TG and uric acid concentrations irrespective of the presence or not of hepatic steatosis, Conclusions: In overweight, high SSB consumers, replacing SSBs with ASBs during 12 weeks did not significantly alter post-prandial TG and uric acid concentration, in spite of the lower energy and fructose content of the meals. These effects were globally the same in subjects without and with hepatic steatosis.

This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU) with glucose alone (GLU) in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol)) underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU) or glucose alone (GLU) to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46). Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p < 0.001) and carbohydrate oxidation lower (18.1 ± 0.8 vs. 24.5 ± 0.8 mg·kg−1·min−1 p < 0.001) in GLUFRU compared to GLU, with decreased muscle glycogen oxidation in GLUFRU (10.2 ± 0.9 vs. 17.5 ± 1.0 mg·kg−1·min−1, p < 0.001). Lactate levels were higher (2.2 ± 0.2 vs. 1.8 ± 0.1 mmol/L, p = 0.012) in GLUFRU, with comparable counter-regulatory hormones between GLUFRU and GLU (p > 0.05 for all). Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen.

PurposeTo characterize the downfield spectrum at 5–10 ppm in the human brain at a high magnetic field of 7 T. Knowledge of relaxation parameters is of interest for spectroscopy as well as chemical exchange–dependent saturation transfer experiments.MethodsWater‐suppressed spectra were recorded as echo time and inversion time series in healthy volunteers to investigate T2 and T1 values of downfield peaks in gray matter at 7T. The spectra were fitted in a two‐dimensional fashion to a heuristic model of a series of Voigt lines, and the relaxation times were obtained for 12 peaks of interest.ResultsThe mean T2 values averaged over the volunteers ranged from 24 to 158 ms, whereas the mean T1 values ranged from 0.22 to 2.40 s. Spectra of specific inversion and echo times revealed superposition of the amide peaks of N‐acetylaspartate with short T2 and an inhomogeneously broadened component with longer T2.ConclusionsT2 values were shorter than expected for most peaks, whereas T1 values had a very wide range; shorter relaxation times for some peaks suggests the presence of macromolecules. Most of the larger peaks seemed to be composed of overlapping components, because the Gaussian widths in the Voigt line shape descriptions were larger than expected based on field inhomogeneities. Magn Reson Med 78:11–19, 2016. © 2017 International Society for Magnetic Resonance in Medicine